Pier Luigi Luisi.2006.The Emergence of Life~From Chemical Origins to Synthetic Biology

T H E E M E R G E N C E O F L I F E

The origin of life from inert chemical compounds has been the focus of much research for decades, both experimentally and philosophically. Connecting both approaches, Luisi takes the reader through the transition to life, from prebiotic chemistry to synthetic biology. This book presents a systematic course discussing the successive stages of self-organization, emergence, self-replication, autopoiesis, synthetic compartments and construction of cellular models, in order to demon-strate the spontaneous increase in complexity from inanimate matter to the first cellular life forms. A chapter is dedicated to each of these steps, using a number of synthetic and biological examples. The theory of autopoiesis leads into the idea of compartments, which is discussed with an emphasis on vesicles and other orderly aggregates. The final chapter uses liposomes and vesicles to explain the synthetic biology of cellular systems, as well as describing attempts to generate minimal cellular life within the laboratory. With challenging review questions at the end of each chapter, this book will appeal to graduate students and academics researching the origin of life and related areas such as biochemistry, molecular biology, bio-physics, and natural sciences. Additional resources for this title are available online at www.cambridge.org/9780521821179.

P i e r L u i g i L u i s i_{became Professor Emeritus (Macromolecular Chemistry) at} ETH-Z¨urich in 1982, where he also acted as Dean of the Chemistry Department; he is currently a professor of Biochemistry at the University of Rome 3. He has authored c.300 papers in the fields of enzymology, molecular biology, peptide chemistry, self-organization and self-reproduction of chemical systems, and models for cells.

T H E E M E R G E N C E O F L I F E

From Chemical Origins to Synthetic Biology

P I E R L U I G I L U I S I University of Rome 3

Cambridge University Press

The Edinburgh Building, Cambridge CB2 8RU, UK

First published in print format

ISBN-13 978-0-521-82117-9 ISBN-13 978-0-511-22094-4 © P. L. Luisi 2006

2006

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Contents

Preface page xi

Acknowledgments xiii

List of books on the origin of life xiv

1 Conceptual framework of research on the origin of life on Earth 1

Introduction 1

Determinism and contingency in the origin of life 4

Only one start – or many? 10

The anthropic principle, SETI, and the creationists 12

Questions for the reader 16

2 Approaches to the definitions of life 17

Introduction 17

A historical framework 19

The visit of the Green Man 23

Main operational approaches to the origin of life 26

I. The “prebiotic” RNA world 27

II. The compartmentalistic approach 29

III. The “prebiotic metabolism” approach 31

Concluding remarks 36

Questions for the reader 37

3 Selection in prebiotic chemistry: why this . . . and not that? 38

Introduction 38

From Oparin to Miller – and beyond 40

Other sources of organic molecules 46

Miller’s␣-amino acids: why do they form? 50

Some notes on homochirality 52

Concluding remarks 56

Questions for the reader 58

4 The bottle neck: macromolecular sequences 59

Introduction 59

Proteins and nucleic acids are copolymers 60

The quest for macromolecular sequences 62

What about polynucleotides? 65

A grain of sand in the Sahara 68

The “never-born proteins” 70

A model for the aetiology of macromolecular sequences – and a

testable one 72

Homochirality in chains 76

Chain chirality and chain growth 78

Concluding remarks 82

Questions for the reader 84

5 Self-organization 85

Introduction 85

Self-organization of simpler molecular systems 87

Self-organization and autocatalysis 91

Polymerization 93

Self-organization and kinetic control 95

Self-organization and breaking of symmetry 97

Complex biological systems 100

Self-organization and finality 105

Out-of-equilibrium self-organization 106

Concluding remarks 109

Questions for the reader 111

6 The notion of emergence 112

Introduction 112

A few simple examples 114

Emergence and reductionism 116

Deducibility and predictability 117

Downward causation 119

Emergence and non-linearity 120

Life as an emergent property 123

Concluding remarks 125

Questions for the reader 128

7 Self-replication and self-reproduction 129

Introduction 129

Self-replication and non-linearity 129

Myths and realities of self-replication 132

Contents ix

One more step towards complexity 141

Self-reproducing micelles and vesicles 143

Concluding remarks 153

Questions for the reader 154

8 Autopoiesis: the logic of cellular life 155

Introduction 155

Historical background 156

Basic autopoiesis 157

Criteria of autopoiesis 159

What autopoiesis does not include 160

Chemical autopoiesis 162

Autopoiesis and cognition 164

Cognition and enaction 167

Necessary and sufficient? 169

One glance further up: from autopoiesis to the cognitive domain 172

Social autopoiesis 175

Autopoiesis and the chemoton: a comparison of the views of Ganti

with those ofM_{aturana and Varela 177}

Concluding remarks 179

Questions for the reader 181

9 Compartments 182

Introduction 182

Surfactant aggregates 182

Aqueous micelles 187

Compartmentation in reverse micelles 189

Cubic phases 198

Size and structural properties of vesicles 199

The water pool and the membrane of vesicles 203

Prebiotic membranes 206

The case of oleate vesicles 209

Concluding remarks 211

Questions for the reader 213

10 Reactivity and transformation of vesicles 214

Introduction 214

Simple reactions in liposomes 214

Giant vesicles 222

Self-reproduction of vesicles 223

The matrix effect 233

Concluding remarks 240

Questions for the reader 242

11 Approaches to the minimal cell 243

Introduction 243

The notion of the minimal cell 244

The minimal RNA cell 246

The minimal genome 247

Further speculations on the minimal genome 251

The road map to the minimal cell. 1: Complex biochemical

reactions in vesicles 254

The road map to the minimal cell. 2: Protein expression in vesicles 259

The road map to the minimal cell. What comes next? 263

Concluding remarks 265

Questions for the reader 267

Outlook 268

References 271

Preface

There are already so many books on the origin of life, as listed on pages xiv–xi. Why then write another?

There are two answers to this question. The first comes from the desire to write a book for students – rather than a specialist book – in which the various phases of the transition to life would be laid out in a discursive way that illustrates the basic principles of self-organization, emergence, self-reproduction, autocatalysis, and their mutual interactions. Another important aspect of this teaching aim is to take into consideration the philosophical implications that are present, more or less consciously, in the field of the origin of life. I believe in fact that the younger generation of chemists and molecular biologists should be more cognizant of the connections between the biological and the philosophical quest, so as possibly to integrate the most basic language of epistemology, and see their science work in a broader dimension. This integration, when taken seriously, may also foster an interaction with the ethical and humanistic aspects of life. The age-old question: “what can science say about the domains of psyche, ethics, or consciousness?” is usually discarded by most scientists with a wave of the hand. This behavior is one of the main reasons why science has lost contact with the broad public – and again, it would be desirable that the younger generations take a different stand. Although this is not a central issue of this book, I hope to offer some hints on how this new approach might be defined.

While all these reasons are centered on the target of teaching, the other reason for the coming to being of this book is more subtle. It comes from the perception of a shift in the field of the origin of life, a new “Zeitgeist” (spirit of time), which makes it timely to propose a new discourse.

One aspect of the new Zeitgeist is the influence of system biology, a new opera-tional framework where the behavior of an entire complex biological system is more important than – or as important as – the individual molecular events. Although the origin of this novel biology lies in the development of analytical tools, more than in

a basic philosophical shift, the final consequence is an operational framework which is at some distance from the reductionistic approach of viewing life as a reaction based solely on nucleic acids. I believe that the exaggerated emphasis given until now to the prebiotic RNA world probably needs to be brought back into balance. And I believe the balance must be based on a more integrative view of cellular pro-cesses, even at the stage of the origin of life. Thus, I will give here proper emphasis to the autopoietic view of minimal life – which is generally not considered in other books. The latter chapters are devoted to the chemical and physical properties of compartments, vesicles in particular, and these are more technical in nature. In fact, this book suffers from that kind of heterogeneity that characterizes the field of the origin of life: on the one hand it thrives on epistemological concepts; and on the other hand it is based on experimental organic and physical chemistry. This double nature, far from being a problem, constitutes the very complexity and beauty of the field.

More generally, I will try to illustrate the different views on the origin of life and early evolution – notions like determinism and contingency will come into focus. All these scientific views are based on the postulate that life on Earth comes from inanimate matter; and a corollary of this postulate is that it might be possible to reconstitute life in the laboratory, at least in some elementary form. The ambition of understanding the prebiotic chemistry leading to the transition to life, and ultimately, to the Faustian dream of making life on the workbench, underlies the whole field – and is also the common thread of this book.

I do not know whether this dream will be fulfilled, but in closing I would like to cite Friedrich Rolle, a German philosopher and biologist, who, in 1863, writing about the hypothesis that life arose from inanimate matter, stated:

The general reasons for this assumption are really so impelling, that no doubt sooner or later it will be possible to show this in a clear and broadly scientific way, or even to repeat the process by experimentation.

This was written one and a half centuries ago and yet today we do not know whether we will ever get there. This book makes no pretence of showing the way, but as the pages unfold we will see some of the reasons why this enterprise is so difficult; and this in itself is a kind of positive knowledge.

Acknowledgments

A number of colleagues were very kind and helpful with their advice. I would like to thank Antonio Lazcano, and Albert Eschenmoser, who in different ways helped me with their frank comments; and Meir Lahav, Joseph Ribo, Jeffrey Bada, and David Deamer. Particular thanks are due to Dr. Pasquale Stano, whose help has been essential, particularly, but not only, with the bibliography; also Rachel Fajella helped with the editing of some parts of the manuscript. I am also particularly indebted to Angelo Merante for the illustrations and the formatting of the manuscript: without him, the manuscript would still be in my drawers. Last, but not least, I want to thank my students of the University of Rome 3, their positive feedback at the very early stages of the manuscript was very important.

Bastian, H. (1872).The Beginnings of Life. Appleton.

Pryer, W. T. (1880).Die Hypothesen ¨uber den Ursprung des Lebens. Berlin. Leduc, S. (1907).Les Bases Physiques de la Vie. Masson.

Osborn, H. (1918).The Origin and Evolution of Life. Charles Schribner and Sons. Oparin, A. (1924).Proishkhozhddenie Zhisni. Moskowski Rabocii. (In Russian, translated

into English as: Oparin, A., 1938.The Origin of Life. MacMillan).

Haldane, J. B. S. (1929), The origin of life. InThe Origin of Life, ed. J. D. Bernal. World Publishing Co.

Bernal, J. D. (1951).The Physical Basis of Life. Routledge and Paul. Oparin, A. (1953).The Origin of Life. Dover Publications.

Haldane, J. B. S. (1954). The origin of life.New Biol.,16, 12.

Schr¨odinger, E. (1956).What is Life? And other Scientific Essays. Cambridge University Press.

Oparin, A. (1957).The Origin of Life on Earth, 3rd edn. Academic Press. Crick, F. (1966).Of Molecules and Men. University of Washington Press. Bernal, J. D. (1967).The Origin of Life. World Publishing Co.

(1971).Ursprung des Lebens. Editions Rencontre.

Fox, S. W. and Dose, K. (1972).Molecular Evolution and the Origin of Life. Freeman. Orgel, L. E. (1973).The Origins of Life. Wiley.

Miller, S. L. and Orgel, L. E. (1974).The Origin of Life on Earth. Prentice Hall. Ponnamperuma, C. (1981).Comets and the Origin of Life. Reidel.

Cairns-Smith, A. G. (1982).Genetic Takeover and the Mineral Origin of Life. Cambridge University Press.

Day, W. (1984).Genesis on Planet Earth: the Search for Life’s Beginnings. Yale University Press.

Cairns-Smith, A. G. (1985).Seven Clues to the Origin of Life. Cambridge University Press.

Shapiro, R. (1986).Origins: A Skeptic’s Guide to the Creation of Life on Earth. Summit. Fox, S. W. (1988).The Emergence of Life. Basic Books.

De Duve, C. (1991).Blueprint for a Cell: The Nature and the Origin of Life. Portland Press.

Eigen, M. and Winkler-Oswatitisch, R. (1992).Steps Towards Life. Oxford University Press.

Morowitz, H. J. (1992).Beginning of Cellular Life. Yale University Press. Margulis, L. and Sagan, D. (1995).What is Life?Weidenfeld and Nicholson.

Books on the origin of life xv

Rizzotti, M., ed. (1996).Defining Life. University of Padua.

Thomas, P. J., Chyba, C. F., and McKay, C P., eds. (1997).Comets and the Origins and Evolution of Life. Springer Verlag.

Brack, A., ed. (1998).The Molecular Origin of Life. Cambridge University Press. Dyson, F. (1999).Origins of Life, 2nd ed. Cambridge University Press.

Fry, I. (1999).The Emergence of Life on Earth. Free Association Books.

Maynard Smith, J. and Szathm´ary, E. (1999).The Origins of Life. Oxford University Press. Varela, F. J. (2000).El Fenomeno de la Vida. Dolmen Ensayo.

Willis, C. and Bada, J. (2000).The Spark of Life. Perseus Publications.

Zubay, G. (2000).Origins of Life on the Earth and in the Cosmos. Academic Press. Schwabe, C. (2001).The Genomic Potential Hypothesis, a Chemist’s View of the Origins,

Evolution and Unfolding of Life. Landes Bioscience.

Day, W. (2002).How Life Began: the Genesis of Life on Earth. Foundation for New Directions.

De Duve, C. (2002).Life Evolving, Molecules, Mind and Meaning. Oxford University Press.

Schopf, J. W., ed. (2002).Life’s Origin, The Beginning of Biological Evolution. California University Press.

Ganti, T. (2003).The Principles of Life. Oxford University Press.

Popa, R. (2004).Between Necessity and Probability: Searching for the Definition and Origin of Life. Springer Verlag.

Ribas de Pouplan L., ed. (2004).The Genetic Code and the Origin of Life. Kluwer. Luisi, P. L. (2006).The Emergence of Life: From Chemical Origins to Synthetic Biology.

1

Conceptual framework of research on the origin

of life on Earth

Introduction

The main assumption held by most scientists about the origin of life on Earth is that life originated from inanimate matter through a spontaneous and gradual increase of molecular complexity.

This view was given a well-known formulation by Alexander Oparin (Oparin,

1924, 1953 and 1957), a brilliant Russian chemist who was influenced both by Darwinian theories and by dialectical materialism. A similar view coming from a quite different context was put forward by J. B. Haldane (Haldane,1929;1954;

1967). By definition, this transition to life via prebiotic molecular evolution excludes panspermia (the idea that life on Earth comes from space) and divine intervention. If we look at Figure1.1without prejudice, we realize that Oparin’s proposition is extremely bold. The idea that molecules, without the help of enzymes or DNA, could spontaneously assemble into molecular structures of increasing complexity, order, and functionality, appears at first sight to go against chemical and thermo-dynamic common sense. This view, which modern biology generally takes for granted, appears in most college textbooks, specialized literature, and mass media. The background of Figure1.1is the continuity principle (Oparin,1924; De Duve,

1991; Morowitz,1992; Crick, 1996; Eigen and Winkler-Oswatitisch,1992; Orgel,

1973; 1994), which sets a gradual continuity from inorganic matter to organic molecules and from these to molecular complexes, up to the onset of cellular life, with no qualitative gap between each stage. In this sense, then, the view expressed in Figure1.1is the modern version of a kind of spontaneous generation, although on a sluggish time scale.

In recent times, the challenges of creationists and their attacks on educational institutions in the United States led to some novel scrutiny of this view. There is nothing new in the arguments of the creationists since the writing by William Paley, the Anglican priest who became famous for having introduced one of the

Cells

Metabolic networks Polymer complexes Macromolecules

Biomonomers Molecules Atoms

Figure 1.1 An arbitrary scale of complexity towards the emergence of life. most famous metaphors in the philosophy of science, the image of the watchmaker (Paley,1802):

. . . when we come to inspect the watch, we perceive . . . that its several parts are framed and put together for a purpose, e.g. that they are so formed and adjusted as to produce motion, and that motion so regulated as to point out the hour of the day; that if the different parts had been differently shaped from what they are, or placed after any other manner or in any other order than that in which they are placed, either no motion at all would have been carried on in the machine, or none which would have answered the use that is now served by it . . . the inference we think is inevitable, that the watch must have had a maker – that there must have existed, at some time and at some place or other, an artificer or artificers who formed it for the purpose which we find it actually to answer, who comprehended its construction and designed its use.

Living organisms, Paley argued, are even more complicated than watches, thus only an intelligent Designer could have created them, just as only an intelligent watchmaker can make a watch. According to Paley (1802):

That designer must have been a person. That person is GOD.

As already stated, modern science – even without reaching the extreme reductionism of Richard Dawkins and his Blind Watchmaker (Dawkins,1990) – does not conform to this view. Paley’s metaphor was already negated in his time by Hume and other contemporary philosophers. This does not mean that all scientists are necessarily atheist: the meeting point (the easy one) between science and religion is to accept the idea of a God, who created the beginning and the laws of nature, leaving them

Introduction 3 alone to do their job. We will come back to this argument a couple of times in this book.

Creationists apart, the view that life originates by itself from inanimate matter is rich with important implications for the philosophy of science and life at large. It is therefore important in our discussion to pause and consider this view, the underlying conceptual framework, as well as some of the consequences.

Let us start with the concept that is perhaps most important for lay people: it may at first sight appear that once divine intervention is eliminated from the picture, nothing remains except molecules and their interactions to arrive at life. Of course, evolution and interactions with the environment are very important factors, and they can take the fancy form of self-organization and emergence. However, all these factors appear to be based on, or caused by, molecular inter-actions. In other words, at first sight the acceptance of the view expressed in Figure1.1is tantamount to stating that life consists only of molecules and of their interactions.

Is it so? Does a rose consist only of molecules and their interactions? We can answer yes, but it is also fair to say that this would represent only a first, gross approximation. First of all, notice that the term “consists of” does not necessarily imply that life can beexplainedandunderstoodin terms of molecules and their interactions. Here comes the age-old question of the discrimination between struc-ture and properties, and whereas the strucstruc-ture per se can be seen as consisting of small parts, usually properties and behavior are not – or at least additional quali-tative concepts are needed. In turn, this does not necessarily mean that life holds something intrinsically unexplainable or beyond the reach of science. This is an important and subtle point, and I hope to be able to offer some clarifying ideas about that in the chapter dealing with autopoiesis and cognition.

Let us consider some of the further implications of Figure 1.1. The view that cellular life can be arrived at from inanimate matter may imply in principle the possibility of reproducing it in the lab. Why not, if all we need is a bunch of molecules in a properly reactive environment? This way of thinking is the basis of the experimental work on the origin of life. In fact, the best way to demonstrate the validity of this view would be to make life in the laboratory – the age-old Faustian dream. We do not know how the process of the transition to life really occurred in nature, so how can we reproduce it in the laboratory? The answer to this question is conceptually simple, as pointed out by Eschenmoser and Kisak¨urek (1996):

the aim of an experimental aetiological chemistry is not primarily to delineate the pathway along which our (natural) life on earth could have originated, but to provide decisive exper-imental evidence, through the realization of model systems (‘artificial chemical life’) that life can arise as a result of the organization of the organic matter.

In other words, since we do not know, each of us is free to choose. Do as you wish so long as you show that it is possible, respecting the prebiotic conditions, to create life from inanimate matter. This is the challenge and the method is open-ended. The ambition of scientists working in the field would be simply to arrive atminimal life: a system containing the minimal and sufficient molecular ingredients to be called alive (this notion will be discussed in detail later on in this book). Of course this also calls into question the definition of life, a difficult issue but not an unsolvable one, as we will also see in thenext chapter.

Whereas almost all researchers on the origin of life would subscribe to one form or another of Figure1.1, with life arising from the inanimate matter, they would not agree with each other as to what is the main motor for the upward movement in the ladder of complexity. This point brings us to thenext section.

Determinism and contingency in the origin of life

Is the pathway that goes from inanimate to animate matter determined by the laws of physics and chemistry? Or is it due to a unique event resulting from the contingent parameters operating in a particular time/space situation – something that in the old nomenclature would be called chance?

The dichotomy between determinism and contingency is a classic theme in the philosophy of science (see, for example, Atmanspacher and Bishop,2002) and in this chapter it will be considered only in the restricted framework of the origin of life (see also Luisi, 2003a).

Thus, a deterministic answer assumes that the laws of physics and chemistry have causally and sequentially determined the obligatory series of events leading from inanimate matter to life – that each step is causally linked to the previous one and to the next one by the laws of nature. In principle, in a strictly deterministic situation, the state of a system at any point in time determines the future behavior of the system – with no random influences. In contrast, in a non-deterministic or stochastic system it is not generally possible to predict the future behavior exactly and instead of a linear causal pathway the sequence of steps may be determined by the set of parameters operating at each step.

Considering first the deterministic point of view, we can refer to Christian de Duve (1991); as an authorative example. In his book on the origin of life he writes:

. . . Given the suitable initial conditions, the emergence of life is highly probable and governed by the laws of chemistry and physics . . .

Determinism and contingency in the origin of life 5

. . . I favor the view that life was bound to arise under the physical–chemical conditions that surrounded its birth . . .

The idea of the high probability of the occurrence of life on Earth, although phrased differently and generally with less emphasis, is presented by other significant authors. For instance, H. J. Morowitz in his well-known book on the emergence of cellular life (1992, p. 12), states:

We have no reason to believe that biogenesis was not a series of chemical events subject to all of the laws governing atoms and their interactions.

He also adds, interestingly (p. 3):

Only if we assume that life began by deterministic processes on the planet are we fully able to pursue the understanding of life’s origins within the constraints of normative science.

And he concludes (p. 13) with a clear plea against contingency:

We also reject the suggestions of Monod that the origin requires a series of highly improbable events . . .

This seems to lead to the idea that life on Earth was inescapable, and in fact Christian de Duve (2002), referring to a sentence by Monod to the contrary, restates this concept (p. 298):

. . . It is self-evident that the universe was pregnant with life and the biosphere with man. Otherwise, we would not be here. Or else, our presence can be explained only by a miracle . . .

Interestingly, this author, a few pages earlier (p. 289), writing about the evolution of life, has to say:

‘Evolution’ . . . main mechanism is by natural selection acting on accidental genetic mod-ifications devoid of intentionality. The finding of molecular biology can leave no doubt in this respect.

This complex and apparent set of contradictions testifies to the inherent difficulties of modern scientists in having a clear-cut view of the situation.

However, as I mentioned, the idea that life on Earth can be seen as a deterministic pathway of highly probable and perhaps inevitable events is to be found frequently in the literature. In this regard, I would like to make a general point.

To say that the natural laws may have governed the prebiotic scenario and all that happened in terms of reactivity and transformations, is one thing. To say that the natural laws have constructed a series of causal steps to lead to life, is another matter; in fact, the latter assumes that the determinism is purposely guided towards the formation of life. The natural laws per se do not have a preferential direction,

and actually they move without a purpose – as de Duve also mentioned above – in the direction of the most probable events. In other words, to invoke a guided deter-minism toward the formation of life would only make sense if the construction of life was demonstrably a preferential, highly probable natural pathway: but this is precisely what we do not know. The statement: “the origin of life must have been highly probable otherwise we would not be here” is certainly not a significant sci-entific statement. Rather, it is significant, only if we accept that it is based on the unconscious faith that life is unavoidable.

In fact, the same position is taken by a considerable number of the more liberal of creationists (as opposed to the biblical creationists, see Sidebox1.1), those who accept the idea that God created the world and the natural laws, however let these laws take their own course. Thus, they can accept the science inherent in the natural origin of life, evolution, and Darwinism. Once the natural laws are given, everything develops accordingly, corresponding to a form of determinism. The problem is, that these creationists must assume that God, having created the natural laws, forcibly and purposely directed them towards the construction of life and mankind. In a way, there is an internal contradiction in this view, as one cannot invoke natural laws with corresponding determinism and then force these laws of nature into one preferential channel.

Is there an alternative to this deterministic view? One of the alternatives would be to invoke a miracle, as the one described for example by Hoyle in a famous metaphor (Hoyle, 1983): the accidental building of an airplane by a tornado whirling through a hangar full of spare parts. Rejecting this conjecture, then, de Duve (1991) claims:

The science of the origin of life has to adopt the deterministic, continuity view – otherwise it would not be possible to adopt a scientific method of inquiry,

echoing the assertions of H. J. Morowitz. This last argument – that we have to adopt the deterministic view, otherwise we are out of business – may sound na¨ıve and tautological, but actually it is tantamount to our definition of science. Science, in its traditionalist and perhaps conservative definition, is the study and interpretation of world phenomenology in terms of the laws of physics and chemistry (with the corollary that science, also by definition, can be seen as a constant internal struggle to expand and overcome its own borders). At any rate, this definition is useful to set a clean, working benchmark between science and non-science. Science is just one part of the human enterprise, and nobody is obliged to belong to the party – but if you do it, you have to accept the more or less uncomfortable definition of science and respect the rules. At this point we should mention the “doc-creationists,” those who adhere to the biblical narrative, that the world was created a few thousand years ago in seven days. One is welcome of course to have this world view, and negate all findings of science, but one cannot be a creationist and a scientist at the

Determinism and contingency in the origin of life 7 same time.1Likewise, one cannot claim to be a Christian and refuse at the same time to accept the Gospel. Either one, or the other. Sidebox1.1, contributed by Margaret Schoeninger, shows the wide diversity of views held within the relatively small creationist movement.

Sidebox 1.1

Margaret J. Schoeninger, Professor of Anthropology The University of California at San Diego

American creationism

In North America a strong attack is being directed toward organic evolution, especially as it relates to humans. Supported by several groups of Christians, largely outside traditionally recognized Christian religions, American Creationism is variable in its arguments although all these rely heavily on the Bible (see excellent review by E. Scott,2004). Most emphasize biblical literalism but one subset believes Earth is young and another believes Earth is old. The former turns to the Bible for all matters including those involving the physical world. Some groups in the former subset allow for limited microevolution (within species changes) but reject all possibility of macroevolution (transformation of one species into another). For them, humans and apes have independent ancestry and Earth’s geology results from a series of catastrophic occurrences like a worldwide flood. Leaders in these movements often come from technical fields like engineering (e.g., Henry Morris of the Institute for Creation Research outside San Diego, California and Walter Brown of the Center for Scientific Creation in Phoenix, Arizona).

Proponents of the second subset, which believes Earth is old (variably), include those who believe that there is a gap in time between sections of the Old Testament accounting for an old Earth, that all of geological history falls within the time before Eden, and the rest is revealed in the Bible. Others believe that the “days” described in Genesis are variable in length (>24 hours), but otherwise everything is revealed in the Bible. Progressives believe that the universe mostly developed according to natural laws, but that God intervened at strategic points along the way with regard to life on Earth. A growing, and increasingly effective group, adheres to the notion of Intelligent Design (well-funded at the Discovery Institute located in Seattle, Washington). In contrast to the other groups, individuals in this group often have post-doctoral degrees

1_{I believe that the main problem of the “doc-creationists” is their inability to distinguish between mythology and}

religion. To illustrate this I include a short personal anecdote. A few years ago I was involved in a public debate of science versus religion, in a church, with a protestant priest in Switzerland. Father S. started first, and read out to his congregation an old Sumerian legend, 600 years older than our Bible, narrating a universal flood, the birth of a child from a virgin, and other episodes very similar to those in our Bible. And then he said to his congretation: “You see, this is mythology. Let’s now get to religion” – leaving me with almost no ammunition. This goes well with the statement by C. von Weizacker who said:the Bible should be taken either seriously or literarily.

(some in science) or other professional degrees, some from major universities. Some have faculty positions in major universities (e.g., P. Johnson, an emeritus professor of law at UC Berkeley). This view includes a supernatural, personal Creator that is proven by the presence of order and intricacy or complexity, who initiated and continues to control the process of creation toward some end or purpose. They oppose science as defined by the Arkansas balanced-treatment case in 1982, that Science is (a) guided by natural law, (b) explanatory by reference to natural law, (c) testable against the empirical world, (d) tentative in its conclusions, and (e) falsifiable.

Macroevolutionary processes are accepted in varying degrees, but the key issue is to have an involved, personal creator. In contrast to the preceding groups, one set of Creationists, including the majority of Protestant seminaries and the Catholic Church, believe in Theistic Evolution. The theory holds that there is a Creator who relies on nature’s laws to bring about a purpose, that the Bible is not to be taken literally, that science is the method of choice to investigate the world, and that evolution is not seen as a contradiction to theism. In their view, science, which is materialistic in its method of investigation, is independent of the realm of ethics and morals. This latter realm is the concern of responsible social constructs, like religion.

Professor Schoeninger grew up in an academic household in extremely

conservative sections of the US (South Carolina and central Florida). Including those formative years, she has lived in 11 of the 50 states. Her BA is from the Florida (southeast), M. A. from the Cincinnati, Ohio (midwest), and Ph. D. from Michigan (midwest). Her faculty positions include: Johns Hopkins Medical School

(mid-Atlantic), Harvard (New England), Wisconsin (northern Midwest) and the University of California in San Diego (west coast) plus a postdoctoral position at the University of California in Los Angeles (west coast). Although her major research interest is the “evolution of human diet”, perhaps this diverse background explains her fascination with American Creationism.

It is also apparent that the anti-Darwinian movement comes not so much from the present and past Pope, but rather from side-kick zealots – see, for example, the short editorial by Holden (Holden, 2005). As for myself, I would be more sympathetic towards the creationists’ camp if experimental evidence were to be provided. It is not difficult to conceive what this should be: simply findequally old fossils of horses, dinosaurs, hominids, snails, cynobacteria, and sword fish. As long as this simple evidence is not forthcoming, it is probably safe to be scientifically very sceptical about the creationistic view (in this sense, it is almost funny that the creationists lament some small gaps in the theory of evolution). If you are interested in the creationist movement in Latin America and Mexico, in particular, see the recent article by Lazcano (Lazcano,2005).

The interesting conjunction in de Duve’s and Morowitz’s view – and all the others who adhere to the deterministic view of the high probability of the origin of life – is the rejection of the miraculous scenario, and the acceptance, more or

Determinism and contingency in the origin of life 9 less, of the notion of the inevitability of life under the deterministic laws of physics and chemistry. I maintain that this view is similar to the (more liberal) creationistic view, although not stated expressly by those authors. I will return to this point later in this section.

The claim of the inevitability of life on Earth is criticized by some authors, for example Szathm´ary calls it the “gospel of the inevitability” (Szathm´ary,2002), and Lazcano (2003) has similar views. This “inevitability” view has its counterpart in the notion that contingency is the basic creative force for shaping the molecular and evolutionistic constructs on Earth (which de Duve,2002, dubbed “the gospel of contingency”). It should be said that de Duve accepts contingency, but in a context other than the origin of life (de Duve,2002).

The contingency view on the origin of life and biological evolution is not new; actually is an old icon in the history of science. One may recall Jacques Monod with hisChance and Necessity(Monod,1971), his colleague Fran¸cois Jacob with The Possible and the Actual(Jacob,1982), and the books by Stephen Jay Gould, who is perhaps the most cited author on contingency in biological evolution (see for example Gould,1989).

Contingency, in this particular context, can be defined as the simultaneous inter-play of several concomitant effects to shape an event in a given space/time situation. In most of the epistemological literature this word has aptly replaced the terms “chance” or “random event” and in fact it has a different texture. In this sense, it should not be confused simply with a “highly improbable event”, as mentioned above in the Morowitz citation. For example, a tile falling on your head from a roof can be seen as a chance event, but in fact it is due to the concomitance of many independent factors such as the place where you were, the speed at which you were walking, the state of the roof, the presence of wind, etc.

The same can be said for a crash in the stock market, or the stormy weather on a particular summer’s day. Interestingly, each independent factor can actually be seen per se as a deterministic factor: the poor condition of the roof predictably determines some tiles sliding off and falling down. However, the fact that there are so many of these factors, each with an unknown statistical weight, renders the event as a whole unpredictable – a chance event. If the contingent conditions are changed – perhaps only one of them – the final result will be quite different. It may happen a week later, or never. It must be added that this view is not against the laws of physics and chemistry, nor is it equivalent to advancing the idea of a miracle, it is just a stochastic view of the implementation of natural laws.

However, the implications are profound. If we were to start the history of bio-logical evolution all over again, says Stephen Jay Gould (Gould,1989),

. . . run the tape again, and the first step from procaryotic to eucaryotic cell may take twelve billions years instead of two,

this implies that the onset of multicellular organisms, including mankind, may have not arisen yet or may never arise. This is contingency in its clearest form. An extreme consequence of this contingency view is Monod’s belief (Monod,1971) that the human species, being a product of contingency, might just as well not have came into existence; hence the famous notion of “being alone in the universe.” As a sympathizer of the importance of contingency, I wish to stress that this “being alone in the universe” should not lead one to deduce that the humanistic and ethical values are deprived of meaning, or that the sacredness of life, if you want to call it that, is impoverished. I believe in the contrary, that the values of consciousness and ethics can be arrived at from within the human construct without the need for transcendental sources.

Can one say a final word about this dichotomy contingency/determinism? it would be wise, of course, to avoid the extremes and look for a balance. The image that comes to mind is one used by Maturana and Varela (1998), when discussing the subject of biological evolution; consistently with Kimura’s views on evolution, they use the metaphor of water falling from the top of the hill: the flow of water is determined by gravity, by the laws of nature. However the actual path is determined by the accidents on the ground – the trees, grooves, and the rocks encountered on the way, so that the actual downhill flow of water is a balance between the forces of determinism and contingency.

Compromises like this are always useful and make life easier. However, often they fail in the most critical situations. For example, take one fundamental question in the origin of life: is there a transcendental power behind it, or not? It would be nice to find a balance, a hybrid between Scylla and Charybdis, but, unfortunately, this is an either/or situation.

Only one start – or many?

I would now like to consider another question partly related to contingency and determinism: whether life started only once in one particular place on Earth or several times in several places. Probably most “determinists” would say that, since life has a very high probability of arising, there is no reason why it should have started only once and only in one magical place. “Only once” is a notion appealing to “contingentists”: if the conditions to start life were the product of contingency – a particular set of chemicals in particular concentrations at particular temperature and pressure and pH etc. . . . – it would be almost impossible to multiply such conditions; this implies that life started only once. This argument is also connected with the question of homochirality, to be discussed later: if life started several times, each time based on contingency, then half of the time we would have one type of homochirality, and half of the time the opposite one. Does the occurrence of only

Anthropic principle, SETI, and the creationists 11 one type of configuration of amino acids and sugar suggest that there was only one start? The answer of the “determinists” would be that the preferred configuration is something “ex lege” (i.e., obligatory by law), and therefore it would happen each time the same way. . . . And generally if life started many times, what then? Well, one argument says that it does not really matter, as these different initial forms of life would sooner or later enter into competition with one another, and the strongest would prevail.

There is however an extreme view of the notion of “life starting many times” that does not comply to this easy scenario. This is the view of C. Schwabe (Schwabe and Warr,1984; Schwabe,2001), which is highly controversial, but worth mentioning nevertheless. He starts from the hypothesis that life comes from a distribution of nucleic acids, and that this distribution was widespread all over Earth, so that there was not one, nor two or three, but multiple starts. He then goes to the extreme of saying that all species on Earth have an independent origin – a billion independent origins. He says (Schwabe,2004):

Multiple origins means multiple species because the energy content of various combinations of nucleotides is the same, so that chemistry has no guide for the de novo synthesis of a defined specific nucleic acid that would give rise to just one species. Many new sequences will produce many origins . . .

Clearly this means a complete rejection of the fundamental Darwinian principle of common descent. Also, he rejects mutation and natural selection as the mechanisms that produced species. Is this view also contrary to the universality of biochemistry, and in particular the monophyletic origin of life, to which most biochemists today would subscribe? Probably yes; but of course if one assumes an absolute deter-minism, then the laws of chemistry and physics would produce the same products at each different start. This goes against the notion of “frozen accident” and the unique origin of the genetic code. So, there was never a time on Earth with only one kind of species, and the development of species was parallel rather than sequential. Of course all these ideas are substantiated by arguments and data – for these, the reader should refer to the original sources.

It should also be mentioned that Schwabe carries this view to the extreme, and he ends up arguing that life is widespread in the whole universe (Schwabe,2002) and that the various stages of biogenesis are thus, in principle, predictable within the realms of quantum chemistry.

Having moderately pleaded for contingency rather than for determinism, I per-sonally feel uneasy with these perspectives; however, aside from the extremes of the Schwabe scenario, the question of multiple origins for the transition to life is a valid one – yet another question, that is valid, beautiful and unanswered.

The anthropic principle, SETI, and the creationists

The notion of the inevitability of life appears to be present in science in many forms. In my opinion the anthropic principle, for example, belongs in this category. This can be expressed in different ways but the basic idea is that the universal constants, the geometric parameters, and all things of the universe are the way they are in order for life and evolution to develop (Barrow and Tipler,1986and1988; Davies,

1999; Barrow,2001; Carr,2001). It is thepost hocargument that since we are so improbable, our presence must signify a purposeful universe.

The anthropic principle can be expressed in more sophisticated forms, but I believe that my simplification given above is not at all far from the target. In fact, one reads in the primary literature, for example in Paul Davies’ book (Davies,1999):

If life follows from (primordial) soup with causal dependability, the laws of nature encode a hidden subtext, a cosmic imperative, which tell them: ‘Make life! And, through life, its by-products, mind, knowing, understanding . . .’

This view is held, although not always expressed as an adherence to the anthropic principle, by several authors in the field. For example Freeman Dyson (1985) writes:

As we look out in the universe and identify the many accidents of physics and astronomy that have worked together to our benefit, it almost seems as if the Universe must in some sense have known that we were coming.

We can even add a citation (Shermer,2003) from Stephen Hawking, a self-defined atheist (in his book, the word “God” appears on almost every other page):

And why is the universe so close to the dividing line between collapsing again and expanding indefinitely? . . . If the rate of expansion one second after the Big Bang had been less by one part in 1010, the universe would have collapsed after a few million years. If it had been greater by one part in 1010_{, the universe would have been essentially empty after a few} million years. In neither case would it have lasted long enough for life to develop. Thus one either has to appeal to the anthropic principle or find some physical explanation of why the universe is the way it is.

It is interesting that the anthropic principle finds more supporters among physicists than biologists, who remain in general rather skeptical about this (see for example Erwin,2003). One general question is whether the extract by Paul Davies and his colleagues can be defined as a scientific argument – or just a claim of faith? One scientific argument that is often used by adherents of the anthropic principle is the ubiquity of biological convergence: the fact that the paths of evolution are relatively few (see for example Conway-Morris,2003). However, it has already been shown by Gould that architectural constraints limit adaptive scope and channel evolutionary patterns, to use the wording of Erwin (2003). See also the modern extension of the

Anthropic principle, SETI, and the creationists 13 anthropic principe into cosmology and the notion of “multiverse” (Livio and Rees,

2005).

There are many counter-arguments to the anthropic principle. For example, things are also the way they are in other parts of the universe, and there also slight changes in geometric distance would bring about cosmic catastrophes. Yet there is no life there. More than anything, I see in the anthropic principle a great tautology. Of course life, being life, is a granted mystery. Somebody once said “If you believe in life, then you can believe anything”. This is a beautiful sentence, but we should not forget that everything that is unknown is a miracle until it is explained: lighten-ing, the phases of the moon, the growth of the rose. In fact, one might ascribe the anthropic principle to the general category of “crypto-creationism” or more gener-ally to the stream of the “inescapability of life” – as it implicitly contains the belief of at least an intelligent design. All this goes back to William Paley’s watchmaker metaphor: as already noted, creationists or those adherent to the intelligent design have said nothing new since then. Many people see the anthropic, or egocentric, view as a position of faith – that things are the way they are in our part of the universe just to permit life. It is a view that is decidedly opposite to the principles of contingency and a view that, implicitly or not, pushes towards natural theology as an explanation for the mysteries of the universe. I repeat here my deep respect for the religious view – it is probably good to keep a little door open; but in doing this it is important not to confuse the boundaries of science and religion.

The argument of the anthropic principle – that the great laws of nature are the way they are otherwise there would be no life – is a truism at many levels. If one considers the atmosphere, there would be no life if there were more oxygen, or less oxygen; or a higher temperature, or a lower one; or less humidity, or more humidity, etc. The same is true in the molecular world. Of course if on Earth there had only been diketopiperazines and not amino acids; or if sugars did not have the size they have; or if lipids were three times shorter, then we would not have life.

This last consideration may lead to a more down-to-earth question: why has a certain type of molecular form been selected in the construction of life – and not another? I consider this type of question more scientifically sound than those of the anthropic principle, because it can be answered on the basis of thermodynamic arguments and because it permits one to perform experiments. For example, why has the five-membered ring ribose been selected out and not, for example, the six-membered piranose ring? To deal with this question in an experimental way is a constructive way of understanding the nature of life. This is the approach taken by Albert Eschenmoser and his group at the Swiss Federal Institute of Technology (ETH) of Z¨urich (Bolliet al.,1997a,b). In one of his essays, Eschenmoser reflects on the relation between cosmic anthropic principle and the fine tuning of chemico-biological life. He considers the specific case of RNA, and writes (Eschenmoser,

. . . the strategy may read as follows: Conceive (through chemical reasoning) potentially nat-ural alternatives to the structure of RNA, synthesize such alternatives by chemical methods, and compare them with RNA with respect to those chemical properties that are fundamental to its biological function.

(See also Eschenmoser,1999). We will come back to this point in the next chapters, dealing with prebiotic chemistry.

Let us consider now another scientific movement that in my opinion seems to operate against the framework of contingency. This is the field of SETI (Search for Extra Terrestrial Intelligence), where scientists are trying to catch signals from the cosmos, believing that there is a finite probability that alien civilizations exist and are willing to communicate with us (Huang,1959; Kuiper and Morris,1977; Sagan,

1985; Horowitz and Sagan,1993; Sagan,1994; Barrow,2001; Wilson,2001; and perhaps you will want to reread the article by G. G. Simpson,1973, on possible alien civilizations). The point I want to make here concerns the cultural background of this research. In fact, with the assumption of intelligent life similar to ours on other planets, the distance from contingency could not be greater. The assumption of intelligent life elsewhere is based on the unproven assumption that the same or a similar set of conditions is operative on that other (unknown) planet. Not only should one then believe in the determinism of life on our planet, but also in a kind of cosmic determinism that leads to the occurrence of life on other planets: determinism squared.1

Again, it is far from my intention to throw a lance at SETI. Personally, I think that this is a great vision, and that visions in science should be encouraged, particularly in an era in which mostly pragmatic and applied research projects find support. My point is rather to emphasize that this movement is also based on the belief that life is inevitable and widespread.

Conceptually close to the idea of SETI is the idea of a general panspermia, which assumes that life on Earth originated elsewhere in the universe and came to us in the form of some vaguely identified germs of life. This view has appealed already to the ancient Greeks, such as Anaxagoras (500–428 BC), right through to Hermann von Helmhotz and William Thomson Kelvin at the end of the nineteen century, to Svante Arrhenius in the beginning of the twenty century and ending with Francis Crick, Fred Hoyle and Chandra Wickramasinghe (1999;2000) in our time; see also Parsons (1996) and, for example, Britt (2000). These different ver-sions have different names, such as Arrhenius’s radio panspermia, Crick’s directed panspermia, ballistic panspermia (meteorites), or modern panspermia from comets (Hoyle and Wickramasinghe). In the more general and poetic version, the theory of panspermia sees life as a general property that permeates the cosmos and therefore

1 _{For an interesting discussion on the relationship between SETI and ID (intelligent design), see the article by}

Robert Camp in the e-mail newsletter of Skeptics, www.skeptic.com, in theSkeptic Magazineof February 16, 2006.

Anthropic principle, SETI, and the creationists 15 does not need to have an origin (Britt,2000; Hoyle and Wickramasinghe, 1999; Shostak,2003). How far can one go with this idea? Wickramasingheet al.recently published a paper in the well-respected medical journalThe Lancetwith the the-ory that SARS has a panspermia origin (see the comments by Ponce de Leon and Lazcano,2003). There is a gray zone between science and science fiction that I personally find fascinating, but is very difficult to navigate without inhibition.

In general, on the issue of contingency versus determinism, the large majority of scientists nowadays are probably on the side of contingency. For most chemists, molecular biologists, and physicists, the notion of contingency is almost trivial. However, it is also true – as we have seen – that a significant part of the scientific population rejects the rationality of contingency and favors a determinist view of the origin of life.

How does one explain this basic dichotomy in the same generation of scientists? An easy way to describe the contradiction is to say that scientists, having pushed God out of the front door, let Him enter again through the back door. More than God per se, I believe it is the notion of the sacredness of life that has sneaked in the back entrance.

In this regard, Carl Gustav Jung’s archetypes of the collective unconscious come to mind. An archetype is the part of the mental structure that is common to all mankind and that, according to Jung and his scholars (von Franz,1988; Meier,

1992), represents the creative matrix of all conscious and unconscious functions. In their exchange of letters (Meier,1992), the well-known physicist Wolfang Pauli and C. G. Jung discuss at length the influence of archetypical mind structures on science. In our specific case, we would have to invoke a collective unconscious struc-ture (the archetype of the sacredness of life?) that influences theWeltanschauung of scientists somehow to maintain the holy nature of life. This archetype would not appear with the same intensity in all scientists, but would be more manifest in those for example who have, or have had, a religious background. Of course, by definition of the unconscious, the beholder is not aware of his own mental behavior.

All these “crypto-creationist” movements tend to negate contingency and chance as the constructors of life and mankind, as reiterated by the following extract from Monod (Monod,1971):

We would like to think ourselves necessary, inevitable, ordained for all eternity. All religions, all philosophies and even part of science testify to the unwearyingly heroic effort of mankind, desperately denying its own contingency . . .

I will return to the controversy between determinism and contingency in Chapter4, taking the concrete example of the sequence of biopolymers.

Questions for the reader

1. Do you accept the view that life on Earth originated from inanimate matter without any contribution from transcendent power?

2. Do you accept the idea that biological evolution is mostly shaped by contingency? If not, what would you add to this picture?

3. Are you at peace with the idea that mankind might not have existed; and with the idea that we may be alone in the universe?

4. Do you accept the idea that a rose is made up only by molecules and nothing else?

2

Approaches to the definitions of life

Introduction

In this chapter two related questions will be considered. Firstly, the definition(s) of life; secondly, the ideas on how to implement such views on life in the laboratory. The idea of defining life is generally met with scepticism or benevolent nods by a large number of scientists. The arguments behind this negative attitude are various: such an enterprise is deemed neither useful nor easy, since everybody knows what life is, but to describe it in words is impossible. A slightly more sophisticated argument is based on the assertion that the transition from non-life to life is a continuous process, and therefore the discrimination between the living and the non-living is impracticable.

This negative attitude has several components, which have been partly analyzed (Luisi,1998). One main problem is that the term “life” is too vague and general, and loaded with a number of historical, traditional, religious values. In particular, in the Christian tradition, the term life is generally linked to the notion of soul – and in Buddhism is linked to the notion of consciousness.

Of course, this is too much of a big picture and to define life at this level may indeed appear impossible. However, one can scientifically tackle this question by looking at life in its simplest expression, namely microbes and other unicellular organisms. This is a first, important clarification, which also eliminates (at least for most scientists) the notions of soul or consciousness from the picture. In other words, let us talk only about microbial life, and try to give a definition of cellular life. Another difficulty in attempting to give a definition of life is that in fact the term “definition” is too ambitious, too frightening. Probably the term “description” would be more acceptable. In the language of epistemology, there is the distinction between anintrinsic description, meaning a context-independent description based on first principles; and anoperational description. As Primas says in a different context (Primas,1998):

. . . by contrast an operational description refers to empirical observations obtained by some pattern recognition methods which concentrate on those aspects we consider as relevant.

Actually, most of the “definitions” of life given in the literature comply to the above operational description. In the following pages, the term “definition” is used mostly as a way of habit, meant however in the above epistemological context.

Even so, there is another clarification to make in order to avoid further confusion on the matter. This is the following: life and its definition have been discussed on two distinct levels. On one level life is considered mainly as agenetic population phenomenon: one generation of E. coli makes the next generation of E. coli; a culture of green peas produces the next green peas family, and so on for all animals and plants. The alternative view of life, familiar mostly to chemists, physicists and to those in the field of artificial intelligence, is that at the level of thesingle individual. A scientist looks at a single specimen (e.g., a novel robot; or a synthetic supramolecular complex; or a single specimen of a new jellyfish; or a specimen of presumed life on a distant planet) and asks the question: is this entity actually living or not? In this case the analysis is focused on one single organism under inquiry; the historical background may be unimportant, since it may be unknown or impossible to establish. This kind of local, “here and now” view is the one that demands a criterion to discriminate between the living and the non-living on an immediate basis – without waiting for reproduction (that particular specimen may be sterile, or may take a thousand years to reproduce . . .).

However it is clear that, even when accepting these three limitations (micro-bial cellular life, the notion of description rather than absolute definition, and the discrimination between genetic and individual life), the question of a definition of life remains a “hairy” problem, mostly because we all have different defini-tions (descripdefini-tions) of life, depending on our own bias and philosophical back-ground. I have observed – and am resigned to – the fact that it is practically impos-sible to bring physicists, chemists, and biologists to an agreement on what life is.

However, I still think – despite these intrinsic difficulties – that it is important to debate the question of the definition of life, both from an intellectual and a practical point of view. Everyone working in the field of the origin of life should be able to provide their own definition (or description) of life, simply because they work experimentally or theoretically on models of minimal life; and they should state and define the subject of the inquiry and the final aim of the work. This corresponds already to a kind of definition of life. Considering the number of authors in the field, this may correspond to quite a large number of different research projects, but all should adhere to the same basic constraints. What are these?

A historical framework 19 Firstly, I believe that any of the above descriptions of minimal life should permit one to discriminate between the living and the non-living. All forms of life we empirically know about should be covered by such a definition – and conversely one should not be able to find forms of life that are contradictory to such a definition. Secondly, there is the intellectual challenge to capture in an explicit formulation the quality of life: how can one express the common denominator of micro-organisms, plants, animals, mushrooms, and mammals which set them apart from the inanimate world of rocks and machines? Clearly, even if we do not arrive at an unique definition of life, the two above conditions are capable of fostering useful discussion and progress in the field.

A historical framework

After these preliminary considerations, we can look at a few definitions of life given in the literature. For a taste of them, the reader may refer to those mentioned in the monographs by Folsome (1979), Chyba and McDonald (1995), or in a book edited by the late Martino Rizzotti (Rizzotti,1996; Popa,2004).

In addition, a few dozen definitions of life are given in over forty pages by a corresponding number of authors, in the book edited by Palyiet al.(2002). They are all different from one another, some very short and some very lengthy. From each, of course, something can be learnt, but the general view is also that each one, without much comparison with previous literature and the corresponding published critical constraints to the field, pretends to have caught the truth. Is it really the case, that there are dozens of different truths on the subject? It all depends, as previously mentioned, on the meaning one wishes to attribute to the term “definition” of life: in particular if one wants to use it as an operational description to make something in the laboratory, or if one wants instead to embark on an intellectual, philosophical definition based on primary natural laws. We will see some more of these two extremes in this chapter. In the previously cited book (Palyiet al.,2002) I would like to bring attention to the interesting paper by Alec Schaerer (2002), who approaches the conceptual conditions for conceiving and describing life, including the aspects of language, cognition, consciousness; and, in terms of originality of thought, also the paper by Kunio Kawamura (2002), who approaches the origin of life from the angle of “subjectivity”, referring to the philosophical work by Imanishi (for me, there are strong ties with the view of autopoiesis, to come later in this book). This author provides then a view of life from the classic Japanese philosophical view, with the notion ofshutaisei(subjectivity). In the same book there is also the Vedanta view of life (Apte,2002) as well as that of the Russian Orthodox tradition (Arinin,2002). There are questions about life: “Is life reducible to complexity?” (Abel, 2002); “When did life became cyclic?” (Boiteau et al., 2002); “does biotic

life exist?” (Valenzuela,2002) . . . All this is just to reiterate the question about life, and the definition of life, elicits answers and input from the most differse human cultures. And from this, one should learn that in order to make sense out of these questions (what is life?; can we give a definition to life?) one should first limit the breadth of the inquiry – for example, limit oneself to defining life by looking at bacteria, and stop here before proceeding further. Go back first to the roots of simplicity. This is the approach we will follow in this book.

Now, let me go back to a few historical notes arbitrarily selected, with the aim of illustrating the historical framework (see also Luisi,1998). Only the naturalistic view of life, excluding the creationistic or transcendental view will be considered. Let’s start with the German biologist and philosopher Friedrich Rolle who noted a long time ago (1863):

The hypothesis of an original emergence of life from inanimate matter . . . can at least offer the advantage of explaining natural things by natural pathways, thus avoid-ing the invocation of miracles, which are actually in contradiction with the foundations of science.

This was about the same time that Darwin himself thought of a naturalistic view of the origin of life: remember his little warm pond full of salts and other good ingredients, which later on would become the famous prebiotic soup? However, Darwin didn’t think too much about the origin of life. Some of the contemporary scientists who popularized his views, however, did it for him, most notably Ernst H¨ackel, who stressed that there is no difference in quality between the inanimate and the animate world (Anorgane und Organismen) and that therefore there is a natural and continuous flux from the one to the other (H¨ackel,1866). This very “continuity principle” was also advocated clearly by Friedrich Rolle (Rolle,1863; Pryer,1880).

Proceeding with the historical discourse, let’s consider a surprisingly acute definition given by F. Engels (yes, as in Engels and Karl Marx) written in1894(!):

Life is the existence form of proteic structures, and this existence form consists essentially in the constant self-renewal of the chemical components of these structures.

This is indeed surprising, given the early date and the fact that Friedrich Engels certainly was not a great biologist, and that at this time nobody had a clear notion of what proteins really were.

We had to wait over fifty years to have a more scientific rendering of Engel’s con-cept. Let’s consider a definition written by Perret in the early 1950s, and reiterated by Bernal in1965:

origin of life,xi,xii,1,3,4,6,10,12,26,30,35,36,

38,39,40,44,55,67,71,72,75,76,86,99,110,

130,133,141,149,152,153,154,178,182,199,

209,237,241,245,259–63,265

Or`o,21,35,40,44,45,47,48,49,50,55,56,206,

207,215,216

and Kimball,40

orotic acid,45,55

oscillating reaction,107,108,109,110

osmotic pressure,238,241

Ourisson and Nakatani,206,207,215

Ourisson,30,40,206,215

Ousfuri,193,194

Out-of-equilibrium systems,106,110

Paechthorowitz and Eirich,62

Palazzo and Luisi,193

Paley,1–3,13

Palindromic,142

palmitoyl and oleoyl CoA,256,263

Palyi,19

panspermia,1,14–15

Pantazatos and Mcdonald,232

PA-P,255,263

Papahadjopoulus,209,218

paralogous genes,250

parasites,244,249

parity violation,53,56,57

Paul and Joyce,140,142,246,269

PCR reaction in liposomes,257,259,260

pegilation,209,219

Penzien,54

peptidase activity,73

peptide,32,33,140,254

coupling,73,219

synthesis,193

template,139

perception,169,181

periodic reaction,109

permeability,184,202,203,204,205,212,214,241,

260

permeable minimal cell,252

peroxidase,221

Perret,20

personal creator,8

Pfammatter, N.,193

PG synthase,253,263

phase diagram,182

phase transitions,201–11

phenomenology,173

philosophy of science,125,126

phosphate,205,214

phosphatidic acid,256,264

phosphatydylcholine,255,263

phosphoatidylethanolamine,206,215

phosphatidyl nucleotides,240

phospholipases,209,219

phospholipids,50,202,206,208,212,215

photonic crystal,95

photosynthetic,167

physical micellar catalysis,146,149

Piaget,156,171

Pietrini and Luisi,193,197,250,251,261,262

Pileni,190,192

P-index,233

pinacyanol chloride,189

piranose,13

Piries,22

Pizzarello,44,48

and Cronin,45,55

and Weber,45,55

pK,115

Pka,209

Plankensteiner,44,72

plasmids,193

Plasson,30,35,40,43

plasticity,167

Platt,113

Poerksen,124,177

Pohorille and Deamer,30,243,244

Pojman,109

Poliovirus,249

political party,175

poly(A),205,215,259,260,267

polycondensation,61,80,198,207,216

polycyclic aromatic hydrocarbons, (PAHs),48,54

polyethylene glycol,209,219

polyisoprene,78

polymer chemistry,95

polymerase chain reaction (PCR),257,264

polymerase,252,258,265

polymerization,65,92,93,95,100

degree,46

of mononucleotides,66,69

polynucleotide phosphorylase,221,260

polynucleotides,62

polypeptide,35,39,62–3,64,65,68,73,77,80

chains,65

synthesis,258,265

poly(Phe),257,258,259,264,265

polyphosphoric acid,207,215

polyprenyl,206

polypropylene,77,84,97

polysaccharides,45,55,78

poly(U),258,264

POPC,199,205,207,214,215,218,219,228,229,

234,235,239

POPC liposomes,81,221,230,236,260

POP-cytidine,202,208

Pope and Muller,85

porphin,42

porphyrin,97,98,99

Portman,198

potassium bromate,108

Pozzi,207,216

pre-added vesicles,237

prebiotic,237,241

chemistry,31–6,38,40,43,45,48,49,54,59,63,

83,111,206

membranes,146,202,206–9

metabolism,31–6

RNA,29,31,153

RNA world,26,27–9,31,83,202,212,246

soup,27,28,32,33,34,36,40,45,49,55,61

synthesis,41

predictability,117

pre-formed vesicles,234

pre-organization,234,235

pre-RNA world,132–3

Prigogine and Lefever,107

Prigogine, Ilya,107,120,121

Prigogine’s theory,105

Primas Hans,17,112,113,116,125,126

primitive atmospheric conditions,36,40

primitive membranes,206

primitive metabolism,33,36,40,44,49,56

probabilities,121

prokaryotic cell,111,249

propylene,60

protein assembly,109

protein biosynthesis,253,258,263,264

protein expression,197,250,251,256,259,260,262,

263,267

in vesicles,xiii,29,259–63,265

protein folding,86,87,88,97,109,250,251,

262

protein processing,250,251,262

protein synthesis,252

protein translocation,250,251,262

protein turnover,250,251,262

protein/DNA cells,246,247

proteinase K,250,262

proteinoids,64

proteins,65,68,232

proteoliposomes,256,263

proteolitic digestion,66,70–1

protocells,152,245

protoenzyme,72

Pseudomonas aeruginosa,124

psi-spectrum,194

psychology,121

Purello,82,98,99

purines,40,45,50,55

pyranose ring,48

pyranosyl-RNA,80

pyrimidine,45,50,66,70

pyrite,33–5,36,40,44

metabolism of,34

Pyun,95

QB replicase,132,256,257,259,263

Quack,53,57

and Stohner,53,57

quartz,54

quasi-species,142–3

quorum sensing,124

Raab,219

racemate,48,53,54,57,82

racemic amino acid,54

racemic vesicles,149

racemization,45,55,65

radical polymerization of vinyl monomers,60

Radzicka and Wolfenden,62

Ramundo-Orlando,220

Rao,206,215

Rasi, Silvia,233,234,235

rate of growth of economy,123

reactions in vesicles,204,205,214–22,240,254,263

Rebek, Julius,136

reciprocal causation,119

recursive coupling,165,173

reducing power,44

reductionism,116,123

redundancy,245,250,251,262

redundant genes,250

referentiality,179

regulation,256,263

Reichenbach,116

religion,7–8

replicase,260

replicating sequences,143

replication of vesicles,260

replicators,152

representational model,156,167

reproducing,24,161,233,235,256,263

restricted environment,182–98,202

Reszka,219

reverse micelles,143,183,189,191,192,193,194,

196,205,213

reverse protease reaction,73

reversibility,90,91

ribbons,202,208

Ribo,54,82,98

ribonucleotide reductase,253,262

ribonucleotides,261

ribose,13,41,78 d_{-ribose,45,50,51,55}

ribosomal proteins,252,253,262

ribosomal RNA,46

ribosomal synthesis of polypeptides,257,259,260

ribosomes,87,102,193,258,265

ribosomial proteins,252

ribozyme,29,133,142,246,247

Rickettsia conorii,250,251,262

Rickettsia prowazekii,250,251,262

right-handed DNA,55,56

right-handed helices,78

Rikken and Raupach,53,57

Ristle and Sherrington,86

Rizzotti, Martino,19

Roux,263

RNA,14,22,27,28,31,50,51,52,102,238,257,259

and DNA,29

and DNA polymerase,252

and DNA synthesis,258,265

aptamer,141

cell,246

encapsulated in fatty acid vesicles,238

folding,122

genes,246,247

MDV-1 template,256,264

RNA (cont.)

polymerase,141,246,253,263

replicase,246

self-replicase,132

self-replication,133

sequences,122

synthesis,252

template,142,260

r-RNAs,254

RNA-ases,253,262

world,18,19,22,26,27–9,36,40,63,132–3,202,

212,246

road map to minimal cell,254,256,259,263,

265

Rode,64,73

Robinson, B.,190,191

Rolle, Freidrich,xii,20

Rose,117,119,126,173

Roseman,206,215

Rotello,136

Roux,255,263

rsGFP,250,262

Rushdi and Simoneit,207,218

Russian Orthadox,19

S. aureus,261

Sada,220

Sagan,14,23

salvage pathway,254,255,256,263,264

Sankararaman,256,263

Sanchez,33,40

sand in the sahara,65,68

Santiago school,158,165,175

SARS,14,15

Satia,64

Sato,44,55

Scartazzini and Luisi,194

Schaerer,19

Schmidli,218,254,256,263,264

Schmidt,54

Schoeninger,7,8

Schopf,35,38,40

Schroeder,112,116,118,119,120

Schurtenberger,194

Schuster, Peter,122

Schuster and Swetina,143

Schwabe,11

Schwarz,62

Schwedinger and Rode,62

sciences of complexity,121–3

second law of thermodynamics,121

Seddon,198

Segre, Anna Laura,30,240

Segre, Daniele,152

Segre, and Lancet,152

self,86

Self-assembly,48,54,82,85,86,87,97,102,115,

202–11,251,262

Self-complementary,136

Self-identity,166

Self-maintenance,162,245,252

self-organization,78–82,83,85,86,87,88,91,95–7,

102,104,105,106,107,109,110,111,120,124,

180,207,218

and autocatalysis,91–2

and breaking of symmetry,97–100

and emergence,85,160

and kineric control,95–7

in non equilibrium systems,106

processes under kinetic control,87

self-organized criticality,106,121

self without localization,160

Self-production,160

Self-referential,164–7

Self-replicating automata,131

Self-replicating, enzyme free chemical systems,

133–41

Self-replicating micelles,171

Self-replicating peptides,139–41,153

self-replicating RNA,27,28,83

Self-replicating, systems,35,40

self-replication,29,67,71,83,129,131,133

and non-linearity,129–31

and self-reproduction,110,129–51,259,265

self-reproducing micelles and vesicles,143–51,153

Self-reproducing reverse micelles,163

self-reproduction of vesicles,205,215

Self-reproduction,51,85,123,129,143,144,151,

154,162,188,207,212,218,222,223,237,241,

242,245,246,252,256,263,264

of micelles and vesicles,143–51,162

of vesicles,222–3

semantic,129

semi-artificial cell,253,254,262,263

semiotic,167

semi-permeable membrane,159,161

semi-synthetic cell,243,259,265,267

sensorium,169,173

sequence paradox,65,68

sequences,65–8

serendipity,194

SETI,12,14

Severin,140

Shakhashiri,109

Shannon information,152

Shapiro,33,35,36,38,40

␤-sheet,97

shell and core replication,246

Shen,44,72

Shenhav, and Lancet,152

Shimkets,246,247,250

Shiner,124

Shutaisei,19

Sievers,136

sigmoid behaviour,149

silicon fluids,123

Sililn,230

Simon,113

Simpson,14

Sismour and Benner,269

size distribution,132,149,211,226,230,231–3,234,

Smith,249

and Iglewski,124

and Venter,249

social autopoiesis,156,175–9

social insects,123,124

social system,103,110,113,120

sociobiology,110

sodium bromate,52,53

sodium chlorate,53,58

sodium cholate,184,203

sodium dedecanoate,184,203

sodium dodecyl sulfate,184,187

sodium laureate,188

sodium taurocholate,184,204

solar cells,95

solid-like state (liposomes),202–11

Solomon and Miller,221

solubilization of proteins in riverse micelles,

193

space groups,54

space mission Cassini,53,58

specifically,197

Sperry,112

spider,168

Spirin,251

spirituality,175

spontaneous aggregation,101

spontaneous formation of vesicles,211

spontaneous generation,1

spontaneous processes,86,102,120,231–3

spontaneous self-reproduction,149

spontaneous symmetry breaking,98

spontaneous vesiculation,201–11

SPREAD,138

square root law of autocatalysis,136

Stadler, Peter,122

Stano,199,209,219,235,237

stationary state,107

stealth liposomes,219

stereoregular biopolymer,97

stereoregular vinyl polymers,77

stereoregularity,77,84,97

stereospecificty,149

steric factors,100–2

stochastic,55,56

differential equations,122

Stocks and Schwarz,48

Strecker synthesis,45

Strogatz,106,121

strong emergence,118,128

stryer,97,102

styrene,60,61

subjectivity,19

submarine vents,46

subunit interaction,86

sugar gradient,156

sugars,41,45,50,55,170

sulfobetain SB12,184,204

super-condensation of the DNA,194

supervenience,113

supramolecular,109,170,203,208

surface,80,81,87,188,202,205,212,213,238

area,185,205,215,237

of liposomes,206,215

surfaces,133

surfactant aggregation,91,93,109,182–98,202,203,

208

Suttle and Ravel,252

Swairjo,184,203

swarm intelligence,86,87,103–4,110,124,160

Swiss Federal Institute of Technology,191

symbiogenesis,232

symbiotic,143

symmetry,80,82

symmetry breaking,47,54–5,82,97

syndiotacic,77,97

synthesis

of lecithin,207,218

of membrane,252,253,263

of peptides,207,215

synthetic biology,xi,153,175–9,243,269

system biology,269

systems,120–3

system theory,160,180

Szathmary and Luisi,132

Szathm`ary,9,22

Szostak,237,238,246,247

T4 phage,102

T7,253,263

T7 DNA,260

T7 RNA polymerase,250,251,260,261,262,263

Tabony,256,263

Taillades,24,35,40,43,65

Takahashi and Mihara,139

Takakura,30

Tb3+_,232 teleology,105

teleonomy,105

TEM,226,257,259

template,67,71,177

template-directed synthesis,66,70–1,134

template effect,235

template RNA,132

terbium/dipicolinate, (DPA) essay,231

Theng,62

theoretical model,26,27–9,246

theory of autopoiesis,164,179

thermodynamic and kinetic factors,12,103,111

thermodynamic control,50,53,56,72,74,85,86,87,

90,101,109,110

thermodynamic hypothesis of Anfinsen,90

thermodynamics of the micelle formation,187

thermophiles,249

thin filament,101

thioester world,35,38

Thomas,138

and Luisi,233,237,239

Thompson and Varela,119

thrombin,67,71

thymine,240

Tjivuka,136

Tm,202,212,213

tobacco mosaic virus,86,102

top-down,119

topoisomerase,55,56,253,262

Tornadoes,110

total surface,205,213

transcendental,126

transcriptase and primase,252

transcription of DNA,253,260,263

transition temperature,202,212

translation,250,251,262

translation factors,250,251,262

Tranter,53,57

trapped,257,259

tree of Knowledge,9,10

Treponema pallidum,250,251,262

Trinks,67,71

triple helix,138

t-RNA,91,239,258,265

t-RNA folding,92

t-RNA phe,72

tropomyosin,101,102,103

troponin,101

Trp-oligomers,207,216

trypsin,221

Tsukahara,64

Tsumoto,253,260,263

tubulation, see microtubulation

turbidity,231,235

Turing, Alan,106,109,131

tyrosinase,221

Ulbricht and Hoffmann,190

Ulman,86

unilamellar vesicles,199–211,214–40

University of Chile,156

University of Santa Cruz, California,208

uracil,41,45,55

urate oxidase,221

urea,45,55,221

Ureaplasma urealyticum,250,251,262

urease,221

Urey, Harold C.,36,40,44

uric acid,221

Uster and Deamer,232

Vaida,54

Valencia,251

Valenzuela,20

Varela, Francisco,23,124,125,143,156,158,

159,160,162,165,166,168,169,172–5,

176

Varela and Luisi,192

Varela and Maturana,171

Varela and Thompson,119

Vedanta,19

Venter, Craig,248,249

vesicle fusion,230

vesicle growth and self-reproduction,202,212

vesicle growth,228,233,235

vesicle radius,205

vesicle self-reproduction,222,223

vesicle size,239

vesicle surface/volume ratio,205,206

vesicles,29,75,88,115,133,147,171,182,184,199,

201,203,207,209,218,257,259

vesicles from POPC/CTAB,240

Vibrio flscheri,124

vinyl chloride,60

virus,86,87,102,133,159

Virus assembly,110

vitalistic principle,126,249

volcanic solfataric,207

volume/surface ratio,205

von Neumann, see Neumann

von Kiedrowski, see Kiedrowski

vortexes,110

Vreizema,95

Wachetersh¨auser,33,35,36,40,43,50

Waks,192

Walde,156,163,205,206,215,221,256,260,263

and Ischikawa,88,206,215

and Mazzetta,220

watchmaker,105

water-in-oil emulsions,196,250,251,262

Water-in-oil compartmentation,196,261

water pool,190,191,192,193,203,204,205,214

water,114,119

Watson and Crick,36,40,240

weak emergence,118,128

Weaver,113

Weber, Andreas,105,160,167,170

Weber and Varela,105

Weight average,234,235

Weiner and Maizels,254

von Weisacker,7

Weissbuch,54,55,56

Weizmann Institute of Science,152

Wendt,138

Wennestr`om and Lindman,187

Westhof,86

Whitesides,85

and Boncheva,85

Wick,222,223

Wickramasinghe, Chandra,14,15

Wilschut,232

Wimmer,249

Wimsatt,112,113,116,117,118

Winfree,108

Woese, Carl,46,244

W¨ohler,35,39

Wong,132

Woodle and lasic,219

xanthine,40

Yao,139

Yaroslavov,232

yeast transcription factor,139

Yomo,30

and Nomura,248,262

and Urabe, 257, 259

Yoshimoto,220

Yuen,48,207,218

Yufen Zhao,72

Zabotinski-Belusov,110

Zamarev,73

Zampieri,xi,180,193

Zeleny,156

Zelinski and Orgel, 131

Zeng and Zimmermann,85

Zeng,88

Zepik,163

Zhabotinsky,108

Zhang and Cech,252

Zhao and Bada,47

Zhu,219

Ziegler,77

Ziegler–Natta, catalyst, 97